B09

In the previous funding period we discovered a maladaptive cortical network dysregulation linked with anxiety behavior as a pathological mechanism in murine neuroinflammation contributing to initiation of neurodegeneration. We now aim at (1) dissecting the causal relation between brainstem pathology and cortical maladaptive hyperactivity, (2) unravelling the relation of local network dysregulation to brain-wide networks, and (3) pharmacologically modulating cortical hyperexcitability and translating our findings to MS patients. These research questions will be investigated:

1. 1. Does the modulation of AMPA receptors have an effect in neuroinflammatory disorders?
   2. Does the reversal of anxiety symptoms prevent neurodegeneration?
   3. What’s the relation between local nework dysregulation in relapsing-remitting MS with brain-wide networks?
   4. Is there a causal relation between brainstem pathology and cortical maladaptive hyperactivity?